The objectives of this proposal are: (1) to define the role of various host immune factors in primary and recurrent infections with oral herpes simplex virus type 1 (HSV-1); (2) to evaluate the effectiveness of transfer factor in reducting herpetic recurrences, and; (3) to attempt to correlate any benefit from these regimens with specific immune responses. Longitudinal immunological, virological and clinical studies will be conducted on individuals: (1) with primary HSV-1 infections; (2) with infrequent HSV recurrences; (3) with very frequent HSV recurrences and in (4) immunocompromised hosts with primary or recurrent HSV infections. Immunological assays include tests for neutralization, passive hemagglutination and IgM, IgA and IgG antibodies to HSV and assays for cell mediated immunity, including lymphocyte stimulation, interferon and leukocyte migration inhibition. Assays for detecting the number of lymphocytes sensitized to HSV-1 and for demonstrating cytotoxicity of lymphocytes to cells with surface HSV antigens will be developed. In addition, isolation of HSV from peripheral leukocytes will be attempted, and the interactions of HSV with macrophages in vitro and the effect of BCG on HSV infection in mice will be studied. These investigations should provide basic information necessary to the possible use of immunoprophylaxis or immunotherapy of a viral infection which afflicts a large number of people and which has been associted with human cancer. BIBLIOGRAPHIC REFERENCES: Shore, S.L., Black, C.M., Melewicz, Wood, P.A. and Nahmias, A.J.: Antibody-dependent cell-mediated cytotoxicity to target cells infected with type 1 and type 2 herpes simplex virus. J. Immunol. 116: 194-201, 1976. Nahmias, A.J., Shore, S.L., Kohl, S., Starr, S.E. and Ashman, R.B.: Immunology of herpes simplex virus infection. Cancer Res. 36: 836-844, 1976.